The first ancient smallpox genomes ever recovered from the Americas come from two people buried in northern Chile during an epidemic that no written record mentions. The genomes do more than confirm that European colonization carried the virus across the Atlantic. They capture variola, the virus that causes smallpox, at a strange moment in its own evolution: a roughly two-century stretch during the height of colonial epidemics when its rate of genetic change slowed several-fold, followed by an acceleration that coincided with the spread of vaccination. Published in Science, the finding is evidence that a pathogen’s evolution can be shaped by human demography as forcefully as by its own biology.
Historians have long known the broad outline. Smallpox reached the Caribbean by 1518, Mexico by 1520, and the northern frontier of the Inca Empire by 1525. In Chile, an outbreak in 1561 is generally regarded as the first confirmed introduction of the disease. The virus then recurred in waves, killing an estimated 3 to 4 million people, possibly more, across the Americas, most of them Indigenous people with no prior immunity. But the written record was produced almost entirely by colonizers, and it is biased: it captures what colonial administrators saw, not necessarily what was happening inside Indigenous communities. For decades this left a nagging gap. Researchers had recovered ancient genomes of Salmonella enterica, parvovirus, hepatitis B, and yaws from colonial-era burials in the Americas, but never smallpox, and the absence of molecular evidence fed quiet doubts about whether the historians had identified the right culprit for the great epidemics.
The new study closes that gap with two naturally mummified individuals from the Camarones 9 cemetery near Arica, in the far north of Chile, a site associated with the Inca sphere and early European influence. The team, led by Bruno Romero González, a doctoral student at Trinity College Dublin, with researchers at the University of Chile and the Universidad de Tarapacá, screened 13 bone samples for ancient pathogens. Two came back positive for variola virus: an adult woman, 30 to 35 years old at death, and a young man, 18 to 20, both identified from femur fragments. The genomes were recovered at 84.851-fold and 3.206-fold average coverage, and they are 99.912 percent identical, strong evidence that the two people died in the same outbreak, of the same circulating strain.
The mummies themselves confirm who the victims were. Their mitochondrial DNA belongs to haplogroups A2 and B2, both pan-American lineages common across the continent today, and statistical tests found no detectable European ancestry. The infection, in other words, was spreading locally among Indigenous people, not merely among newly arrived colonists. Radiocarbon dating of hair from one individual, calibrated with a correction for the marine component of the coastal diet, combined with molecular clock estimates from the viral genomes themselves, places their deaths between 1492 and 1631, squarely in the early colonial period. The researchers dated the divergence of this now-extinct lineage, which they call CAM9, to around 1296, placing it evolutionarily between early medieval European strains and the lineages that gave rise to the smallpox of the 17th through 20th centuries. The virus arrived with colonialism, and its closest relatives were European.
The discovery was partly an accident of preservation. The bone samples were collected in the 1990s for human ancestry studies, not pathogen hunting, and the human DNA in them was terribly degraded. The viral DNA survived far better. The serendipity extends to a long-standing puzzle at the site: skin lesions on some Camarones mummies, one to five millimeters across and concentrated on the trunk, had been attributed to chronic arsenic exposure, which is endemic in the region’s water and soils. The authors suggest some of those lesions may instead have been smallpox pustules, and that the community experienced both exposures at once.
The deeper surprise is in the virus’s evolutionary tempo. Across the variola family tree, host specialization proceeds by gene inactivation: genes that become dispensable in a virus that lives only in humans accumulate disabling mutations, and the authors count roughly one to two such events per century along early branches. That tempo held in the CAM9 lineage until the mid-16th to early 17th centuries. Then, for about two centuries, from the late 16th to the late 18th century, the pace of change collapsed. Synonymous substitutions, the neutral tick of the molecular clock, dropped 3.1- to 3.8-fold compared with other branches, while protein-altering changes fell less sharply, and the ratio of the two rose. No new gene inactivation events became fixed after the mid-16th to early 17th centuries. The authors interpret this as evolutionary stasis: a virus that had reached a highly optimized relationship with its human host, spreading through millions of immunologically naive people so successfully that there was little pressure to change. When vaccination began to spread in the 19th century, immunity rose, and the substitution rate rebounded.
That interpretation is contested. Hendrik Poinar, an evolutionary geneticist at McMaster University who was not involved in the work, argues that viruses do not really stop evolving; they constantly adjust to host defenses. He suggests the Chilean strain may instead have been less virulent than the smallpox that came later, and notes that even a comparatively mild virus would have had an extreme impact on a population with no prior exposure. Either way, the mummies document something the archives could not: an outbreak that moved through an Indigenous community in the Inca sphere, far from the epidemics described in colonial chronicles, with no written trace.
The finding also raises the question of how smallpox reached Chile’s far north so early. The researchers note that the precise geographical origin of the CAM9 lineage cannot be inferred, and that they cannot exclude the possibility that the ancestor of all 20th-century strains also crossed the Atlantic during the same period. Spread may have followed Indigenous trading networks that long predated European arrival, a route invisible to the colonial record. For modern infectious disease research, the study is a reminder that population movement, immunity, and public health measures are evolutionary forces in their own right, as relevant to influenza, COVID-19, and mpox as they were to the virus that killed millions in the Americas. Two mummified people, buried in an epidemic no one wrote down, turned out to be carrying the answer.
References
Bruno Romero González et al., The genomic identity of early smallpox in South America. Science 393, 504-508 (2026). DOI: 10.1126/science.aee6957.
Lizzie Wade, Ancient DNA confirms historical accounts of how smallpox got to the Americas. Science, 30 July 2026.
Trinity College Dublin, Ancient smallpox genomes reveal how European colonisation brought the disease to the Americas. EurekAlert! press release, 30 July 2026.
Adithi Ramakrishnan, Ancient mummy DNA connects smallpox to European colonization. Associated Press, 30 July 2026.